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Fucoidan Induces ROS‐Dependent Apoptosis in 5637 Human Bladder Cancer Cells by Downregulating Telomerase Activity via Inactivation of the PI3K/Akt Signaling Pathway
Author(s) -
Han Min Ho,
Lee DaeSung,
Jeong JinWoo,
Hong SuHyun,
Choi IlWhan,
Cha HeeJae,
Kim Suhkmann,
Kim HeuiSoo,
Park Cheol,
Kim GiYoung,
Moon SungKwon,
Kim WunJae,
Hyun Choi Yung
Publication year - 2017
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21367
Subject(s) - fucoidan , telomerase , pi3k/akt/mtor pathway , apoptosis , protein kinase b , cancer research , chemistry , signal transduction , microbiology and biotechnology , biology , biochemistry , gene , polysaccharide
Preclinical ResearchFucoidan, a sulfated polysaccharide, is a compound found in various species of seaweed that has anti‐viral, anti‐bacterial, anti‐oxidant, anti‐inflammatory, and immunomodulatory activities; however, the underlying relationship between apoptosis and anti‐telomerase activity has not been investigated. Here, we report that fucoidan‐induced apoptosis in 5637 human bladder cancer cells was associated with an increase in the Bax/Bcl‐2 ratio, the dissipation of the mitochondrial membrane potential (MMP, Δψm), and cytosolic release of cytochrome c from the mitochondria. Under the same experimental conditions, fucoidan‐treatment decreased hTERT (human telomerase reverse transcriptase) expression and the transcription factors, c‐myc and Sp1. This was accompanied by decreased telomerase activity. Fucoidan‐treatment also suppressed activation of the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling enhanced fucoidan‐induced apoptosis and anti‐telomerase activity. Meanwhile, fucoidan treatment increased the generation of intracellular ROS, whereas the over‐elimination of ROS by N ‐acetylcysteine, an anti‐oxidant, attenuated fucoidan‐induced apoptosis, inhibition of hTERT, c‐myc, and Sp1 expression, and reversed fucoidan‐induced inactivation of the PI3K/Akt signaling pathway. Collectively, these data indicate that the induction of apoptosis and the inhibition of telomerase activity by fucoidan are mediated via ROS‐dependent inactivation of the PI3K/Akt pathway. Drug Dev Res 78 : 37–48, 2017. © 2016 Wiley Periodicals, Inc.